Is DLG2 p.Ser519Phe (c.1556C>T) pathogenic?

DLG2 p.Ser519Phe (c.1556C>T) is classified Uncertain significance in DLG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: likely benign (0.094); Absent from gnomAD v4.1.

How common is DLG2 p.Ser519Phe (c.1556C>T) in the general population?

DLG2 p.Ser519Phe (c.1556C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLG2 p.Ser519Phe (c.1556C>T)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

DLG2 p.Ser519Phe

c.1556C>T · rs2542730931 · VCV3082768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 147 kb · p 0.76 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S414F vs ClinVar S519F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLG2
Protein: p.Ser519Phe
Coding: c.1556C>T
MANE Select: NM_001142699
dbSNP: rs2542730931
Type: single nucleotide variant
Location: chr11:83874429 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.93 · 2 PDB

Full DLG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG2 p.Arg797= Benign ★★ same type
DLG2 p.Gln944= Benign ★★ same type
DLG2 p.Leu459= Benign ★★ same type
DLG2 p.Leu514Pro Likely benign ★★ same type
DLG2 p.Lys59= Benign ★★ same type
DLG2 p.Ser804= Benign/Likely benign ★★ same type
DLG2 c.624+1G>A Uncertain significance ★ same type
DLG2 p.Ala128Pro Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dlg2-p-ser519phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown